Institute of Nuclear Physics of Lyon

Tissue-nonspecific alkaline phosphatase (TNAP) is a ubiquitous enzyme whose substrates are various phosphorylated extracellular molecules including pyridoxal phosphate (vitamin B6) and adenine nucleotides. Dysfunctions of TNAP result in hypophosphatasia, a rare disease characterized by defective bone mineralization and impaired brain functions. In the brain, TNAP expression peaks during development and is associated with various steps of neurogenesis. However, the influence of TNAP activity on neurogenesis remains poorly understood in its cellular and molecular aspects. Here we used the SK-N-SH D human neuroblastoma cell line as a cell culture model to further investigate the involvement of TNAP in neuronal precursor proliferation and neuronal differentiation. We also used 1H-NMR-based metabolomics to investigate the molecular correlates of TNAP action on SK-N-SH D cell proliferation and differentiation. We first observed an increase in alkaline phosphatase (AP) activity when the cells were placed in differentiation medium. We next found that inhibiting TNAP with a specific inhibitor (MLS-0038949) impeded neuroblastoma cell proliferation. TNAP inhibition also hindered neuronal differentiation, as evidenced by a decrease in the number of neurite-bearing cells. In contrast, neurite length was not affected by TNAP inhibition, suggesting that TNAP controls neurite sprouting, but not neurite outgrowth per se. The metabolomic results indicate that proliferation and differentiation are associated with a decrease in the amounts of proteinogenic amino acids as well as that of compounds potentially involved in lipid production. This analysis also revealed that proliferation and differentiation are associated with increased glutathione levels and decreased amounts of hypotaurine and taurine, supporting proposals that organosulfur compounds play an important role in these processes. Since pyridoxine was present in the culture media, these results suggest that TNAP is involved in neurogenesis through mechanisms in addition to its role in vitamin B6 metabolism and may instead involve the ectonucleotidase activity (or an unidentified activity) of TNAP.

Flavourful extensions of the Standard Model aimed at explaining its fermionic mass structure typically rely on symmetries, broken at high-energy scales far beyond the reach of foreseeable direct collider searches. We illustrate, using a $SU(2)$ flavour gauge group, that the breaking of these symmetries up to scales as high as $10^7$ GeV could generate a gravitational-wave signal potentially observable by future observatories. We use dimensional reduction techniques to obtain the finite-temperature effective potential and study the possible first-order phase transitions. We match these transitions to steady-state hydrodynamical solutions in order to determine the corresponding gravitational-wave spectra. We observe that order-one gauge couplings are always required for a first-order phase transition to occur. On the other hand, adding leptoquarks (as an example of particles that are typically present in a complete flavour theory) significantly extends the testable parameter space. We find excellent prospects at the Einstein Telescope for future gravitational-wave detection of flavoured $SU(2)$ early-universe phase transitions.

We describe the effort to characterize gravitational-wave searches and detector sensitivity to different types of compact binary coalescences during the LIGO-Virgo-KAGRA Collaborations' fourth observing run. We discuss the design requirements and example use cases for this data product, constructed from $>4.33\ifmmode\times\else\texttimes\fi{}{10}^{8}$ injections during O4a alone. We also identify subtle effects with high confidence, like diurnal duty cycles within detectors. This paper accompanies a public data release of the curated injection set, and the Appendixes give detailed examples of how to use the publicly available data.

The problem of ordering of radial vs.\ orbital excitations is reviewed. It is shown that the current quark models cannot explain the location of the Roper resonance which is slightly lower than the lowest negative-parity excitations. We also study some related spectral problems, such as the dependence of the energies on the quark masses, and the possibility of bound states in simple chromelectric models.

Respiratory-induced organ motion is a technical challenge to radiation therapy for lung cancer. Breathing is controlled by two independent muscles: the thorax and diaphragm muscles. The modeling of their action constitutes an important step for the respiratory motion model. The amplitude of the diaphragm forces and ribs displacement are patient-specific and depends on geometrical and physiological characteristics of the patient. This article presents a patient-specific bio-mechanical model (PSBM) of the diaphragm, as well as ribs kinematics. To determine the appropriate values of specific diaphragm forces for each patient, during a whole respiratory cycle, inverse finite element (FE) analysis methodology has been implemented to match the experimental results to the FE simulation results. Ribs kinematics extracted and calculated directly from 4D Computed Tomography (CT) scan images. We have investigated the effect of element type, finite deformation and elasticity on the accuracy and computation time. The results demonstrate that the proposed FE model including ribs kinematics can accurately predict the diaphragm motion with an average surface error in diaphragm/lungs contact region less than 2.2±2.1mm. This constitutes first steps for biomechanical patient-specific of the respiratory system modeling to pilot lungs and lung tumor motion for External Beam Radiation Therapy (EBRT).

International audience

Astrophysical observations provide compelling evidence for gravitationally interacting dark matter in the universe that cannot be explained by the standard model of particle physics. The extraordinary amount of data from the CERN LHC presents a unique opportunity to shed light on the nature of dark matter at unprecedented collision energies. This Report comprehensively reviews the most recent searches with the CMS experiment for particles and interactions belonging to a dark sector and for dark-sector mediators. Models with invisible massive particles are probed by searches for signatures of missing transverse momentum recoiling against visible standard model particles. Searches for mediators are also conducted via fully visible final states. The results of these searches are compared with those obtained from direct-detection experiments. Searches for alternative scenarios predicting more complex dark sectors with multiple new particles and new forces are also presented. Many of these models include long-lived particles, which could manifest themselves with striking unconventional signatures with relatively small amounts of background. Searches for such particles are discussed and their impact on dark-sector scenarios is evaluated. Many results and interpretations have been newly obtained for this Report.